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OBJECTIVE:
The intralesional injection of recombinant human epidermal growth factor (EGF-IL), a new therapy, has been claimed to prevent major amputations in advanced diabetic foot lesions. In this study, the efficacy of EGF-IL on advanced diabetic foot ulcers (DFU) was reviewed.
METHODS:
Intralesional 75 ?g EGF application (Heberprot-P? 75, Heber Biotec, Havana, Cuba) to 12 diabetic foot lesions in 11 patients (8 males, 3 females; mean age: 62.2?10.6 years) was evaluated. Most of the patients had undergone revascularization and received hyperbaric oxygen therapy (HBOT) and negative pressure wound therapy (NPWT), along with standard care, but failed to heal. After amputation was offered as the final option, EGF-IL was applied to evaluate its effects.
RESULTS:
Two patients underwent amputation, while 10 lesions of the remaining 9 patients healed completely.
CONCLUSION:
Our results prove that intralesional application of EGF can prevent amputations in advanced diabetic foot cases with an ischemic component. However, evidence in the literature supporting its use remains lacking, and its high cost presents an additional problem. Thus, we believe that intralesional application of EGF should be an option for ischemic wounds only after vascular evaluation (and intervention when possible), HBOT, NPWT, and standard care have proven insufficient.

BACKGROUND:
Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012.
OBJECTIVES:
To determine whether autologous PRP promotes the healing of chronic wounds.
SEARCH METHODS:
In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions.
DATA COLLECTION AND ANALYSIS:
We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias.
MAIN RESULTS:
The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I2 = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I2 = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I2 = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I2 = 0%, low quality evidence from 3 trials, 102 participants).
AUTHORS' CONCLUSIONS:
PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.

Diabetic foot ulceration is a major complication of diabetes mellitus. Recombinant human epidermal growth factor (rhEGF) is used topically in the treatment of diabetic foot ulcers. This meta-analysis was designed to evaluate if rhEGF increased the complete healing rate of diabetic foot compared with controls. We searched the MEDLINE, Cochrane Library, EMBASE, and Web of Knowledge databases (up to December 22, 2015). Studies were identified and selected, and data were extracted by 2 independent reviewers. A total of 4 randomized controlled trials including 294 patients were identified. The studies evaluated the rate of healing of diabetic foot that were treated with rhEGF or controls. On account of study heterogeneity, a random-effects model was performed, and the combined odds ratio (OR) indicated a significantly greater complete healing rate in patients treated with rhEGF compared to placebo. The ORs ranged from 1.66 to 14.64, with a combined OR of 4.36 (95% confidence interval = 1.48-12.81, P = .007). These results indicate that rhEGF is efficacious in the treatment of diabetic foot ulcers by increasing the rate of wound healing. These findings support the use of rhEGF in treating diabetic foot.

Diabetic foot ulcer is considered a major health problem that predisposes to limb amputation. Among the different methods to achieve ulcer healing, platelet rich plasma (PRP) gel is gaining popularity. It is thought to stimulate wound closure by providing essential growth factors for healing. This study aims to evaluate the value of autologous PRP gel in the treatment of diabetic ulcers.
PATIENTS AND METHODS:
The study included 56 patients of both sex from 18 to 80 years, with clean chronic diabetic foot ulcers divided into 2 equal groups. The first group was treated by antiseptic ointment dressing and the second group by autologous platelet gel. PRP together with thrombin were prepared by centrifugation at each dressing session. Thrombin and calcium chloride were used to activate the PRP. The formed platelet gel was applied to the wound twice weekly.
RESULTS:
Statically significant increase in healing rate was found in the PRP treated group and complete healing was achieved in 86% of them in comparison to 68% of the control group. In the study group, rate of healing per week was greater during the first 8 weeks and starts to decline afterward. The use of platelet gel showed a lower rate of wound infection.
CONCLUSION:
Autologous platelet gel is more effective than the local antiseptic dressing in terms of healing rate and prevention of infection in clean diabetic ulcers.

The aim of present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of DFU during the first 4 weeks of the treatment. In this longitudinal and Single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria which 70 (70% of them) patients were enrolled in the trial. After the primary caring actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2ml/cm2 of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-value<0.05 were considered statistically significant. The mean (SD) of DFU duration was 19.71 (4.94) weeks for units sampling. The ratio of subjects who withdraw from the study was calculated to be 2 (2.8% of them) of patients. Average area of 71 ulcers in mentioned number of cases was calculated 6.11 cm2 (SD: 4.37). Also, the mean, median (SD) of healing time was 8.7, 8 (SD: 3.93) weeks except for 2 mentioned cases. According to one sample T-test, wound area (cm2) significantly decreased to 51.9 (CI: 46.7-57.1) % through the first four weeks of therapy, averagely. Furthermore, significant correlation (0.22) was not found between area of ulcers and healing duration (p-value>0.5). As results showed, PRP could be considered as a candidate treatment for non-healing DFUs by preventing future complications such as amputation or death in this pathological phenomenon.

The aim of the present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of diabetic foot ulcer (DFU) during the first 4 weeks of the treatment. In this longitudinal and single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria; of these 100 patients, 70 (70%) were enrolled in the trial. After the primary care actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2 mL/cm2 of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-value < 0.05 were considered statistically significant. The mean (SD) of DFU duration was 19.71 weeks (4.94) for units sampling. The ratio of subjects who withdrew from the study was calculated to be 2 (2.8%). Average area of 71 ulcers in the mentioned number of cases was calculated to be 6.11 cm2 (SD: 4.37). Also, the mean, median (SD) of healing time was 8.7, 8 weeks (SD: 3.93) except for 2 mentioned cases. According to one sample T-test, wound area (cm2), on average, significantly decreased to 51.9% (CI: 46.7-57.1) through the first four weeks of therapy. Furthermore, significant correlation (0.22) was not found between area of ulcers and healing duration (p-value > 0.5). According to the results, PRP could be considered as a candidate treatment for non-healing DFUs as it may prevent future complications such as amputation or death in this pathological phenomenon.

The purpose of this study is to determine the safety and effectiveness of Resticutis for the treatment of Wagner's Grade II/III diabetic foot ulcers in comparison with Platelet-Rich and Platelet-Poor Plasma preparations.

Background: Recently the world health organization reported a global prevalence of diabetes exceeding 300 million people, predicting a further 60-70% increase by the year 2030, which means India alone will have 100 million people by the year 2030.Wound healing is problematic in diabetic patients. Encouraging results have shown that PDGF application is better than good wound care alone. But the evidence to demonstrate the safety and efficacy of PDGF in diabetic ulcer is scanty.

Methods: The present study was carried out at PSG Hospitals, Coimbatore, Tamil Nadu, India for a period of one year, where 50 patients with diabetic foot ulcers were included in the present study. Prospective randomized controlled trail was designed for the study. 50 patients with diabetic foot ulcers admitted in surgery wards at PSG Hospitals over a period from August 2011 to August 2012. 25 patients were in the study/treatment group, 25 patients were in the control group.

Results: Out of 50, patients, 25 took treatment in the form of conventional normal saline dressings and 25 took treatment with rh - PDGF dressing once a day. Glycaemic control and adequate control of infection was maintained in both the groups. X-ray foot was taken for all patients and bony involvement was excluded. The initial area measurement was taken on day 01 and final area measurement on day 15 was taken on transparent sheet. Plannimetry was used to measure the outcome that is the target ulcer area using a transparent graph sheet. Results were calculated by using student ‘t’ test.

Conclusions: The wounds in the study group treated with rh-PDGF dressing contracted more than the wounds in the control group (38.55% Vs 12.79%; P≤ 0.001- statistically significant) which indicates rh-PDGF dressing is an effective modality to facilitate wound contraction in patients suffering from diabetes. Rh-PDGF dressing is found to be more effective, safe promoter of wound healing and can be used as an adjunct to saline dressing for healing of diabetic wounds and healing of ulcers receiving PDGF was significantly faster as compared to ulcers receiving placebo.

BACKGROUND:
Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity.
METHODS:
Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use.
RESULTS:
The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 108.
CONCLUSION:
This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers.

Diabetic foot ulcers (DFUs) are associated with an increased risk of secondary infection and amputation. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing several cytokines and growth factors, is known to promote wound healing. However, the effect of PRF on diabetic wound healing has not been adequately investigated. The aim of the study was to investigate the effect of PRF on skin wound healing in a diabetic mouse model. Platelet-rich fibrin was prepared from whole blood of 8 healthy volunteers. Two symmetrical skin wounds per mouse were created on the back of 16 diabetic nude mice. One of the 2 wounds in each mouse was treated with routine dressings (control), whereas the other wound was treated with PRF in addition to routine dressings (test), each for a period of 14 days. Skin wound healing rate was calculated.Use of PRF was associated with significantly improved skin wound healing in diabetic mice. On hematoxylin and eosin and CD31 staining, a significant increase in the number of capillaries and CD31-positive cells was observed, suggesting that PRF may have promoted blood vessel formation in the skin wound. In this study, PRF seemed to accelerate skin wound healing in diabetic mouse models, probably via increased blood vessel formation.

AIMS:
Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head to head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors.
METHODS:
Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio [95% confidence interval] was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA).
RESULTS:
A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of wound infection, cellulitis, peripheral edema and lower limb amputation compared to standard of care.
CONCLUSION:
To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

AIMS:
Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head to head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors.
METHODS:
Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio [95% confidence interval] was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA).
RESULTS:
A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of wound infection, cellulitis, peripheral edema and lower limb amputation compared to standard of care.
CONCLUSION:
To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

OBJECTIVE:
Platelet-rich plasma (PRP) has been proposed as an adjunct for the treatment of foot ulcers in patients with diabetes, as well as a treatment for chronic and acute wounds. This study examined the application of PRP in the treatment of diabetic foot ulcers (DFUs) in patients.

METHODS:
This prospective study was conducted between 2011 and 2014. We used PRP, produced by a kit, for the treatment of DFUs. Patients were allocated to one of three groups, according to size of ulcer. The significance of changes in time for wound healing were statistically assessed.

RESULTS:
The study was completed by 150 patients, and a total of 150 foot ulcers were assessed. Wound size reduction was detected in patients after four weeks of treatment. In DFUs with a 2-5.5 cm2 surface area, complete closure happened after 7.2 weeks, 5.5-8.5cm2 DFUs completely closed after 7.5 weeks, and 8.5-12.5cm2 DFUs healed completely after 8.8 weeks. None of the wounds reopened after eight months of monitoring.

CONCLUSIONS:
This study will provide more evidence for the use of autologous PRP for DFUs in patients.

INTRODUCTION:
It has been demonstrated that plasma growth factor (PGF) responsible for proliferation of smooth muscle cells and fibroblasts significantly shortens treatment duration.

AIM:
To determine the role of human growth factor in the healing of ulcers due to ischaemic diabetic foot syndrome (DFS) following previous angioplasty of the blood vessels of the lower leg and foot.

MATERIAL AND METHODS:
The study group included 50 patients with ischaemic diabetic foot complicated by lower leg ulcers in which angioplasty of the stenotic arteries in the distal lower leg and foot was performed. It has been assumed that the area of the ulcer cannot exceed 5 cm2. Following surgical debridement, each patient received platelet-rich plasma in the form of dressings applied on an ulcer, followed by hydrocolloid dressings. Each dressing was replaced after 10 days, and this procedure was repeated after 20 and 30 days of treatment. The control group included 50 patients with ischaemic diabetic foot complicated by an ulcer up to 5 cm2. Angioplasty of the lower leg arteries was also performed in this group. However, after surgical debridement, wounds were covered with hydrocolloid dressings.

RESULTS:
After 3 months of combined treatment, all wounds in the study group healed whereas in the control group, only wounds of the smallest size healed.

CONCLUSIONS:
Combined treatment of ulcers due to ischaemic DFS with endovascular procedures to re-establish blood flow to the vessels and dressings with autologous platelet-rich plasma significantly shortens the healing time.

Purpose This study aimed to compare platelet-rich plasma (PRP) versus conventional ordinary dressing in the management of diabetic foot wounds.
Background Diabetic foot wound treatment poses a considerable burden on the medical system, with long waiting times for healing in the public hospital system. PRP enables efficient treatment of many patients with hemostatic, anti-inflammatory, and analgesic substances.
Patients and methods This prospective study was focused on 80 diabetic feet wounds. Patients were divided into two groups: group A received conventional ordinary dressing (N=40, 50%) and group B received PRP dressing (N=40, 50%). The mean follow-up period was 12 weeks.
Results The estimated time of wound healing was 12 weeks for 82.5% of the patients in group A and 97.5% of the patients in group B; the PRP group was found to be more effective with fewer complications, less infection, exudates, pain, and failed healing: 17.5, 12.5, 32.5, and 2.5% versus 27.5, 42.5, 62.5, and 17.5% in group B, respectively (P=0.001). The highest healing rate was observed for both groups at the fourth week, but it was better for the PRP group (group B): 0.89±0.13 versus 0.49±0.11 cm2/week in group A.
Conclusion There have been considerable advancements in the use of PRP in therapeutic processes in recent years in tissue regeneration therapy. PRP is a powerful tool for the treatment of chronic wounds and very promising for diabetic foot wounds; PRP enables healing, and reduces infection rates and exudates.

Background Diabetic foot ulcer is a major complication of diabetes mellitus. Over the recent years, great progress has made in the techniques of wound healing, among which autologous platelet-rich plasma (PRP) has attracted the most substantial attention. Platelets are known to start the wound healing process through the release of locally active growth factors. The evidence from studies of autologous PRP to support its use in wound healing is not robust, and further rigorously designed blinded trials are needed. The aim of the study was to evaluate the efficacy and safety of the autologous PRP for diabetic foot ulcer in a randomized control multicenter double-blind design.
Patients and methods The study included 50 patients with diabetic foot ulcers, who were divided into two groups: PRP and platelet-poor plasma (PPP) groups. The PRP group was treated with autologous PRP in gel form as a dressing. The PPP group was treated with autologous poor plasma as a dressing. The frequency of dressing change for each group was twice weekly.
Results The healing rate of the PRP group was found to be significantly higher than that of the PPP group. The healing rate per week of the PRP group was significantly higher than that of the PPP group. The rate of complete healing was significantly higher in the PRP group than that of the PPP group.
Conclusion Autologous PRP is effective and safe for treatment of diabetic foot ulcer.

OBJECTIVE:
To evaluate the role of platelet-rich plasma (PRP) in healing diabetic fool ulcers (DFUs), and to compare the rate of healing and final outcome with conventional therapy.

METHOD:
A prospective study conducted between October 2013 and July 2015. Participants were divided in to two groups: a study group in which PRP was used and a control group receiving standard therapy. Wound assessment was carried out according to the Bates-Jensen Wound Assessment Tool at 0, 7, 14, 21 and 28 days.

RESULTS:
A total of 55 patients were recruited to the study. There were 29 patients in the study group and 26 patients in the control group. After application of PRP, there was significant improvement in mean wound score and significant percent improvement in wound score in the study group (p<0.0001). Complete healing occurred in all patients in the study group in (mean score and standard deviation) 36.7±3 days compared with 60.6±3.7 days in the control group (p<0.0001). There were no unwanted side effects in patients using the PRP in this study.

CONCLUSION:
PRP appears to be a promising agent in the management of DFUs. In this study, DFUs healed more quickly in the study group than in the control group. There was also significant percent improvement in wound score as compared with debridement and dressing only. If proper selection criteria are applied, PRP could be a useful aid to wound healing in people with DFUs.

Background: Diabetic foot ulcers continue to pose significant global issue despite the advances made in the management of diabetes. It causes major foot complications if they are not addressed properly. It needs multidisciplinary approach for its care. While several advancements has taken place in wound care management, platelet rich plasma and stem cell therapy promises to offer a new hope in its management, aiding in cellular and tissue regeneration. The purpose of the present study was to compare Platelet-Rich Plasma versus conventional dressing in the management of diabetic foot ulcers.

Methods: This prospective study was focused on 20 diabetic foot ulcers, carried out in a surgical unit of ACS Medical College and Hospital, Chennai, Tamil Nadu, from January 2018 to June 2018. Patients were divided into two groups; Group A received conventional ordinary dressing (N=10, 50%) and Group B received PRP dressing (N = 10, 50%). The mean follow-up period was 8 weeks.

Results: The estimated time of wound healing was 8 weeks and healing was found to be more effective for patients in group B compared to patients in group A; the PRP group was found to be more effective in wound healing with fewer complications, less infection, exudates and pain.

Conclusions: There have been considerable advances in the use of PRP in therapeutic processes in recent years in tissue regeneration therapy. PRP is a powerful tool for the treatment of chronic wounds and very promising for diabetic foot wounds; PRP enables healing, and reduces amputation rates, infection and exudates.

METHODS:
A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level I-IV investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were "platelet rich plasma", "diabetes", "ulcers", and "wound". The Modified Coleman Methodology Score (MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.

Platelet‐rich plasma (PRP) is widely used nowadays in different fields of medicine, affecting physiological processes including tissue regeneration. The use of PRP in maxillofacial surgical interventions and its efficiency in the improvement of postoperative wound healing were analysed. Patients undergoing plastic and reconstructive surgeries in the maxillofacial region were recruited: 50 patients were enrolled into a control group (received no PPRP injection) and 50 patients were enrolled into a treatment group, where PRP was applied during the surgical procedure. Evaluation of treatment outcomes was carried out by determination of IL‐1β, TNFα, and IL‐6 cytokines levels in the wound‐drain fluid. The stages of wound healing were assessed by cytological analyses and ultrasound within a month period. The use of the PRP has substantially positive effects, contributing to the improvement of the healing process. In the treatment group, fibroblasts, macrophages, and collagen fibres appeared and their quantities increased earlier than when compared with control group patients. The concentration of IL‐1β and TNFα in wound fluid on day 1 and day 5 after operation was higher for the treatment group as opposed to the control group, which was linked to the influence of PRP on inflammatory and granulation phases of the healing process. An ultrasound examination showed less oedema and infiltration in the tissues around the wound of the treatment group.

Aim of work: To assess the healing of diabetic foot ulcers attributed to newly technique preparation of platelet-rich
plasma (PRP) compared with that in the control group with conventional procedures. Methods: A prospective study was carried out between January 2016 to July 2017 on 80 patients suffered from
chronic diabetic foot ulcer not responding to the traditional treatment. Patients were classified into 2 groups:- group
A; included 42 patients that were treated by application of autologous PRP prepared by minimal cost technique and
group B; including 38 patients that were treated with the traditional methods of ulcer management.
Results: Mean ulcer area and ulcer volume in group (A) before treatment were 15.7 cm2 and 14.1 cm3 respectively
while in group (B) were 16.49 cm2 and 14.01 cm3 respectively. Healing rate was (83.33%) in 35 patients in group (A)
and (28.95%) in 11 patients in group (B). No patients suffered from any undesired effects that were directly related to
PRP treatment apart from minimal skin irritation around the ulcer if the dressing was infrequently changed.
Conclusion: Autologous platelet-rich plasma combined with conventional treatment methods accelerates healing
process of diabetic foot ulcers. Easily prepared PRP is safe and cost-effective with reasonable results.

In this observational study performed during 45 months we evaluated patients with chronic and recalcitrant diabetic ulcers who were treated with homologous platelet gel.
Methods
platelet gels were obtained from homologous platelet concentrates that were aliquoted and freezed, being then activated with calcium gluconate and applied in the ulcer after cleaning and debridement.

We evaluated patient's comorbidities, wound characteristics (size, tissue, inflammatory signs, pain), number and time of treatment as well as outcome (classified as complete epithelialization; partial improvement- 50% reduction in wound size or pain relief; no evolution).

Results
Fifty-two patients (42 males, 10 females), with a median age of 65 years (range 43–85) were proposed for platelet gel. The following associated comorbidities were observed: hypertension (n = 41), dyslipidemia (n = 29), polyneuropathy (n = 30), peripheral arteriopathy (n = 32), retinopathy (n = 21), nephropathy (n = 15), cardiac ischemic disease (n = 14), obesity (n = 9). Thirty-eight patients presented with 3 or more associated comorbidities. The more frequent ulcer locations were sole of the foot (n = 13) and heel (n = 10). The median number of applications was 16, during 8.5 weeks. Nineteen patients (44%) achieved complete healing, 3 patients (7%) had a partial response and 21 (49%) had no progression. We did not observe a statistically significant relationship between patient age and response nor between number of comorbidities and response. We observed a more favorable evolution in patients with good compliance and good glycemic control.

Conclusion
Platelet gel is an effective therapeutic alternative, provided compliance and effective metabolic control are ensured.

Foot ulcer is a major complication of diabetes mellitus and often precedes leg amputation. Among the different methods to achieve ulcer healing, the use of platelet-rich plasma, which is rich in multiple growth factors and cytokines and may have similarities to the natural wound healing process, is gaining in popularity. A systematic review with meta-analyses was performed to evaluate the safety and clinical effectiveness of platelet-rich plasma for the treatment of diabetic foot ulcers compared to standard treatment or any other alternative therapy. The electronic databases Medline, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials were consulted in March 2017 with no restrictions placed on the publication date. Predefined criteria were used to determine inclusion of studies and to assess their methodologic quality. Eight randomized clinical trials and two prospective longitudinal-observational studies with control group were included. Platelet-rich plasma treatment increased the likelihood of chronic wound healing (RR = 1.32; 95% CI: 1.11, 1.57, I2 = 15%) while the volume of the ulcer (MD = 0.12 cm2 ; 95% CI: 0.08, 0.16; p < 0.01; I2 = 0%) and time to complete wound healing (MD = -11.18 days; 95% CI: -20.69, -1.68; I2 = 53%) decreased. Regarding safety profile, platelet-rich plasma did not differ from standard treatment in terms of probability of occurrence of wound complications (RR = 0.57; 95% CI: 0.25, 1.28; I2 = 0%) or recurrences (RR = 2.76; 95% CI: 0.23, 33.36; p = 0.43; I2 = 82%) but it decreased the rate of adverse events (RR = 0.80; 95% CI: 0.66, 0.96; p = 0.02; I2 = 0%). Cumulative meta-analysis revealed that there is enough evidence to demonstrate a statistically significant benefit. However, studies included presented serious methodologic flaws. According to the results, platelet-rich plasma could be considered a candidate treatment for nonhealing of diabetic foot ulcers.

In this observational study performed during 45 months we evaluated patients with chronic and recalcitrant diabetic ulcers who were treated with homologous platelet gel.

METHODS:
platelet gels were obtained from homologous platelet concentrates that were aliquoted and freezed, being then activated with calcium gluconate and applied in the ulcer after cleaning and debridement. We evaluated patient's comorbidities, wound characteristics (size, tissue, inflammatory signs, pain), number and time of treatment as well as outcome (classified as complete epithelialization; partial improvement- 50% reduction in wound size or pain relief; no evolution).

RESULTS:
Fifty-two patients (42 males, 10 females), with a median age of 65 years (range 43-85) were proposed for platelet gel. The following associated comorbidities were observed: hypertension (n = 41), dyslipidemia (n = 29), polyneuropathy (n = 30), peripheral arteriopathy (n = 32), retinopathy (n = 21), nephropathy (n = 15), cardiac ischemic disease (n = 14), obesity (n = 9). Thirty-eight patients presented with 3 or more associated comorbidities. The more frequent ulcer locations were sole of the foot (n = 13) and heel (n = 10). The median number of applications was 16, during 8.5 weeks. Nineteen patients (44%) achieved complete healing, 3 patients (7%) had a partial response and 21 (49%) had no progression. We did not observe a statistically significant relationship between patient age and response nor between number of comorbidities and response. We observed a more favorable evolution in patients with good compliance and good glycemic control.

CONCLUSION:
Platelet gel is an effective therapeutic alternative, provided compliance and effective metabolic control are ensured.

Background: With the increase in the prevalence of diabetic foot ulcer (DFU), the demand for optimal treatment and management strategies has risen too. Objectives: Our study investigated the wound-healing effect of platelet-rich plasma (PRP) on DFU and the correlations between the various factors affecting DFU treatment. Methods: 10 diabetes patients with grade 1 DFU were treated using PRP prepared from the patients’ blood (collected using a commercial kit, MyCells Autologous Preparation kit®, Holon, Israel). The ulcer margins were biopsied before and after PRP treatment. Hematoxylin and Eosin staining and immunohistochemical staining for HIF-1α and CD31 were performed to confirm angiogenesis. Spearman’s correlation tests were performed to determine the correlations between the treatment period and various clinical factors. Results: The mean PRP treatment period was 29.4 days. PRP was administered a mean of 3 (1-6) times. The time taken for a 50% reduction in the wound area was 16 days. Among the clinical factors, the presence of calluses in the lesion prolonged the pretreatment period, and significantly reduced the duration of PRP treatment. After PRP treatment, on CD31 staining, the number of endothelial cells was significantly increased. However, on HIF-1α, there was no significant difference. Conclusion: We found that PRP can contribute to wound regeneration through neovascularization. PRP therapy, with various growth factors, is expected to be another treatment option for DFUs.

BACKGROUND:
This randomized clinical trial was conducted to assess the role of platelet-rich plasma (PRP) gel as a treatment of clean non-healing diabetic foot ulcer (DFU) in comparison with regular dressing with saline as a control.

METHODS:
Patients with DFU were randomly assigned to one of two equal groups: group I received dressing with PRP gel and group II received regular saline dressing. The main outcomes of the study were percent reduction in the dimensions of the DFU, healing of DFU, and complications at 20 weeks of follow-up.

RESULTS:
Twenty-four patients were included to the study. The mean age of patients was 55.2 ± 6.4 years. Only three (25%) patients in group I achieved complete healing versus none of group II patients. In total, 8.3% of group I and 41.6% of group II patients did not show any response to treatment. The percent of reduction in the longitudinal and horizontal dimensions of the DFU was significantly greater in group I than group II (43.2% vs 4.1%) and (42.3% vs 8.2%), respectively. The time required to maximum healing was significantly shorter in group I than group II (6.3 ± 2.1 vs 10.4 ± 1.7 weeks, P < 0.0001).

CONCLUSION:
The use of PRP gel as a dressing for chronic DFU resulted in a more significant reduction in the size of the ulcer when compared to regular saline dressing. Also the time to reach the point of maximal possible healing with the least wound dimensions was significantly shorter when using PRP as a dressing protocol.

OBJECTIVE:
To investigate the effectiveness of local injection of autologous platelet-rich plasma (PRP) in treatment of diabetic foot ulcer.

METHODS:
Between October 2017 and October 2018, 90 diabetic foot ulcer patients who met the selection criteria were randomly divided into 3 groups: PRP injection group (group A, PRP was injected and hydrogel dressing covered the wounds), PRP covered group (group B, PRP gel and hydrogel dressing covered the wounds), and the control group (group C, hydrogel dressing covered the wounds), 30 cases in each group. There was no significant difference in gender, age, injured side, disease duration, preoperative glycosylated hemoglobin, wound size, and Wagner grading between groups (P>0.05). The frequency of treatments and hospitalization day in all groups and the total amount of PRP application in groups A and B were recorded. The wound healing condition was recorded during the treatment, and the wound healing rate was calculated at 3 months after the first debridement.

RESULTS:
The frequency of treatments in groups A, B, and C were (10.2±0.8), (11.4±0.6), (12.5±0.5) times, respectively. The total amount of PRP application of groups A and B were (306±24) and (342±18) mL, respectively. There was no significant difference in the frequency of treatments and the total amount of PRP application between groups (P>0.05). The hospitalization days of groups A, B, and C were (40.5±1.8), (62.1±2.3), and (88.6±1.4) days, respectively, showing significant differences between groups (P<0.05). In the course of treatment, the necrosis and exudation of the wounds gradually reduced, the areas of wounds gradually reduced; and the above conditions of group A were significantly better than groups B and C, and group B was better than group C. At 3 months after the first debridement, the wound healing rates of groups A, B, and C were 93.2%±0.8%, 52.1%±1.1%, and 21.3%±1.3%, respectively, with significant differences between groups (P<0.05).

CONCLUSION:
PRP can effectively promote the repair of diabetic foot ulcer. The effectiveness of local injection of PRP is superior to the local coverage.

Introduction
Type 2 diabetes is one of the most prevalent diseases throughout the world. The foot ulcers are severe complications of this disease. Foot ulcers induce the high rate of morbidity, impair quality of life, bring about extreme costs to health service providers, and give rise to waste of time. Recently, platelet-rich plasma (PRP) and platelet gel (PG) have been used for the treatment of chronic wounds. In the present randomized, double -blind, placebo-controlled study, platelet gel derived from umbilical cord blood (UCB) was used to heal the diabetic foot.

Method
The patients were randomly divided into three groups, under the categories of PG, platelet-poor plasma (PPP) and lubricant gel (placebo) (ratio 1:1:1). The processes of gels application were launched for the subject of each group twice per week with 3-4 days’ interval. This mechanism protracted for eight weeks. After completion of 8 weeks, the patients were followed up after two weeks and then continued for nine months with one -month interval.

Result
30 patients underwent statistical analysis. Except for diastolic blood pressure which was significant between groups, there were no statistically significant differences in patients’ baseline demographics. No significant differences were detected between groups at baseline of wounds (P = 0.09). The results revealed that there is no statistically significant interaction among three groups during follow- up time.

Conclusion
The present study provides evidence that there are no significant differences in the size of wound among PG, PPP, and placebo group.

This study evaluated the cost-effectiveness of platelet-rich plasma (PRP) added to usual care versus usual care alone in elderly patients with chronic diabetic foot ulcer (DFU) from the Spanish health care system perpective. A 6-state Markov model with 3-month cycles was used to estimate costs and outcomes of wound healing and risk of recurrences, infections, and amputations over 5 years. Three treatment strategies were compared: (a) usual care plus PRP obtained with a commercial kit, (b) usual care plus PRP obtained manually, and (c) usual care. Data on effectiveness were taken from a recent meta-analysis. Outcomes and costs were discounted at 3% and resources were valued in 2018 euro. Compared with usual care, the PRP treatment with the manual method was more effective and less costly (dominant option), whereas the PRP treatment with the commercial kit was more effective but also more costly, with the incremental ratio being above the cost-effectiveness threshold (€57 916 per quality-adjusted life year). These results are sensitive to the price of PRP kits (a 20% discount would make the PRP treatment a cost-effective option) and effectiveness data, due to the heterogeneity of primary studies. In conclusion, PRP treatment for DFUs could be considered a cost-effective or even cost-saving alternative in Spain, depending on the method of obtaining the PRP. Despite the dominance of the manual method, its general use is limited to hospitals and specialized centers, whereas PRP kits could be used in primary care settings, but their prices should be negotiated by health authorities.

BACKGROUND:
Several randomized controlled trials comparing platelet-rich plasma to standard wound care for chronic wounds have been published. Previous articles have revealed that the role of platelet-rich plasma in promoting chronic wound healing is uncertain. This quantitative meta-analysis was conducted to evaluate whether superior outcomes can be obtained by using platelet-rich plasma in nonhealing ulcers compared with traditional wound care.

METHODS:
The PubMed, EMBASE, EBSCO (Cumulative Index to Nursing and Allied Health Literature), and Cochrane databases were searched through November of 2018 for randomized controlled trials comparing platelet-rich plasma to standard wound care for chronic wounds. For binary outcome measures, we calculated the risk ratio. The continuous outcomes were expressed as the mean differences. Subgroup analyses were also performed according to the type of chronic ulcer.

RESULTS:
Overall, 630 adult patients in 15 randomized controlled trials from 2000 to 2018 were included. The number of ulcers healed in the platelet-rich plasma group was higher than in the control group, and the difference was statistically significant (risk ratio, 1.26; 95 percent CI, 1.11 to 1.42; p = 0.0003). During the fourth week of follow-up, the number of ulcers healed in the platelet-rich plasma group was significantly greater than in the control group (risk ratio, 3.50; 95 percent CI, 1.80 to 6.81; p = 0.0002).

CONCLUSIONS:
Platelet-rich plasma is a valuable and safe treatment dressing for chronic nonhealing ulcers; it is simple to prepare and has remarkable effects. Further high-quality prospective studies are necessary to validate these results.

Platelet Lysate Promotes the Healing of Long-Standing Diabetic Foot Ulcers: A Report of Two Cases and in vitro Study
Hanan Jafar et alHeliyon. 2020 May 4;6(5):e03929

Long-standing foot ulcers present a great challenge in diabetes care. Platelet products have been suggested as a possible therapeutic option. However, nor the effect of an injectable form of platelet lysate on the healing of ulcers nor that on primary cells of the epidermis have been studied. In the current study, we present two cases of an ongoing clinical trial showing the positive effect of autologous platelet lysate injected perilesional. Both clinical cases treated with injections of hPL showed complete healing of previously un-healed within 8 weeks of treatment. Further, we describe the in vitro effect of human platelet lysate (hPL) on primary human epidermal keratinocytes (HEK) in terms of chemotaxis, migration and proliferation. In vitro, HEK showed enhanced chemotaxis towards the hPL compared to keratinocyte-defined media (p < 0.0001). Their migration was also stimulated especially at hPL concentration of 10%V/V (p < 0.0001). In contrast, hPL significantly inhibited HEK proliferation measured through MTT assay (p < 0.0001). In conclusion, the findings presented here provide preliminary evidence of an explanatory mechanism for the effect of hPL on primary keratinocytes and therefore of their potential use in a clinical setting. hPL promotes keratinocyte migration and therefore closure of foot ulcers.